The development of innovative measurement tools can provide new information on brain function, often allowing a range of novel questions to be addressed. Proteomics is one such exciting new tool. NIDA called for the establishment of neuroproteomics centers with several major objectives, including: (1) to provide neurobiologists with the ability to benefit from proteomics experiments, (2) to build a cadre of proteomics experts who will develop expertise in analyzing neural tissues, and (3) to develop new or improve existing proteomics technologies as they relate to neurobiology or tissues of the nervous system. The UIUC Neuroproteomics Center on Cell-Cell Signaling addresses these three key areas. The Center specifically provides peptidomics, proteomics and bioinformatics technologies to the UIUC and national neuroscience communities while simultaneously advancing the performance of state-of-the-art proteomics technologies to new levels of performance. The Center is built around the overarching theme of cell-cell signaling. Extracellular signaling peptides and proteins-neuropeptides, trophic factors, cytokines, and hormones-represent a critical part of the cell proteome that has been implicated in almost all aspects of organism function; they influence behavior, learning and memory, and addiction phenomena. The Center is divided into three scientific cores: the Sampling and Separation Core, the Protein Identification Core, and the Bioinformatics Core, plus the Administrative and Users Cores. There are twelve major users representing 28 individual grants, with their Center research projects concentrating on three overarching scientific thrusts: (1) signaling peptide discovery, (2) relating peptide signaling to function, and (3) non-traditional aspects of cell-cell communication, including glia to neuron signaling and dendritic/axonal RNA transport. The high level of synergy between the neuroscientists and technologists ensures progress in this broad suite of projects, and offers tremendous promise for advancing our knowledge of how systems of neurons interact in both the healthy nervous system and on exposure to drugs of abuse.